涎腺分泌性癌7例临床病理分析

目的 探讨涎腺分泌性癌（Mammary Analogue Secretory Carcinoma,MASC）的临床病理特征、诊断标准及鉴别诊断。方法 收集我院从2011年至2018年117例涎腺恶性肿瘤,由两名高年资病理医师根据2017年版WHO头颈肿瘤分册中所描述MASC镜下形态学特征从中筛选出符合MASC形态特征的病例7例,分析其临床病理特点,运用免疫组化EnVision法检测S-100、Vimentin、CK7、GATA-3、Mammaglobin、P63、Ki-67、CD117及DOG1。结果 7例MASC病例,发生于腮腺6例,颌下腺1例,女性2例,男性5例（男女比例2.5:1）,发病年龄21-63岁,平均和中位年龄分别为45.1岁和44岁,临床症状为颌下区缓慢增大的无痛性肿块,病程2周至3年;7例均为单发结节,直径1.3-3.5cm,平均直径2.77cm,2例结节界限清楚,5例与周围涎腺分界不清;组织学形态显示肿瘤呈多结节状,结节被纤维组织分隔,肿瘤细胞排列成腺管状,微囊样及实性,2例具有乳头状结构,腺腔及微囊内可见嗜酸性分泌物,类似甲状腺滤泡,肿瘤细胞呈圆形、卵圆形,细胞核圆,可见小核仁,胞浆嗜酸性或空亮,核分裂象少见;7例病例均弥漫强阳性表达CK7、Vimetin、Mammaglobin及S-100,强弱不等地表达GATA-3,均不表达P63、DOG1及CD117,Ki-67增殖指数均较低（2%-15%）。7例病例,4例获得随访资料,3例失访,随访时间8-43个月,均无肿瘤复发。结论 MASC是临床罕见的低度恶性涎腺型肿瘤, 易与涎腺腺泡细胞癌（Acinic cell cancinoma,AciCC）混淆,结合组织学形态、免疫表型及基因检测可与AciCC鉴别。     

涎腺分泌性癌临床病理特征分析并文献复习(附4例)

目的:研究并探讨涎腺分泌性癌(secretory carcinoma, SC)的临床病理特征、免疫表型、鉴别诊断、治疗及预后。方法:对4例涎腺分泌性癌进行HE染色和免疫组化染色,收集分析4例涎腺分泌性癌的临床资料并复习相关文献。结果:4例肿瘤均发生在腮腺,患者年龄为30岁～55岁,中位年龄为40岁;肿瘤直径为0.5 cm～3.0 cm;肿瘤组织均界限清楚,2例大部分切面灰白实性,质地中等;1例切面实性,灰粉灰黄相杂,质软易碎;1例呈囊实性改变,实性区质软灰粉色。镜下观察,肿瘤细胞排列成多种结构,可呈微囊、大囊及腺管内乳头状排列。肿瘤细胞界限不清,胞浆丰富,呈嗜酸性或空泡状,具有圆形或卵圆形的细胞核,核仁明显,核分裂象及坏死少见。4例肿瘤细胞CK5/6、p63均为阴性表达,肿瘤细胞均弥漫强表达S100、Mammaglobin,弥漫表达CKAE1/AE3、CK7、CK8、Vimentin,大部分肿瘤区域DOG1表达缺失,仅在少数瘤巢周或腔缘弱阳性,而Ki67增殖指数约10%。结论:发生于涎腺的分泌性癌类似于乳腺的分泌性癌,是一种少见的低度恶性肿瘤,由于其典型的形态学特征,并结合免疫组化结果...     

乳腺腺样囊性癌3例临床病理分析并文献复习

目的：探讨乳腺腺样囊性癌的病理形态学特点及ER，PR,p53，C-erb-B2的表达与其预后。方法：观查和分析3例乳腺腺样囊性癌的病理形态学特征，免疫组化染色表达并进行文献复习。结果：镜检病变形态与涎腺的腺样囊性癌相似，组织学上分为筛孔型、管状-小梁型和实体型三种类型。3例免疫组化均显示ER（-），PR（-），C-erb-B2（-），除1例p53（＋）外，另2例p53（-）。结论：发于乳腺的腺样囊性癌较罕见，预后良好，需与乳腺的筛状型导管内癌和筛状癌、分泌型癌病变鉴别。     

食管原发性腺样囊性癌的临床病理分析

目的 探讨食管腺样囊性癌（ACC）的临床病理特征、组织来源及预后。方法 应用HE染色、免疫组化及组织化学染色，对3例食管腺样囊性癌进行病理及临床分析。结果3例食管腺样囊性癌的癌组织主要由立方形腺上皮细胞和变异的肌上皮细胞组成，呈筛孔状腔隙、管状、实体状排列，腔隙内含嗜碱性和嗜伊红分泌物；3例食管腺样囊性癌中例1表面上皮有移行；免疫组化：3例CK、H-CK、P63、S-100（浆，核）、EMA、Bcl-2均（＋），例3CerBb-2（±），P53（＋），例2CD117（＋），AAT（±）、SMA（-），PAS／AB（＋）。结论 发生在食管的腺样囊性癌很少见，诊断标准及组织细胞起源建议严格定义，起源于唾腺的诊断腺样囊性癌，凡起源于其它部位或组织者应冠以腺样囊性癌。     

涎腺腺泡细胞癌5例报道并文献复习

目的探讨涎腺腺泡细胞癌的临床病理学特征和预后相关因素。方法回顾性分析5例涎腺腺泡细胞癌的临床资料、组织学形态和免疫表型,并复习相关文献。结果男1例,女4例。肿瘤位于口腔牙龈1例,腮腺4例。临床表现为生长缓慢无痛性肿块4例,另1例肿瘤近期生长迅速,偶有疼痛。镜下观察:组织学形态4例呈乳头囊状型,肿瘤细胞形态温和;1例实性伴微囊型肿瘤浸润性生长伴点灶状坏死,肿瘤细胞异形明显,呈高级别转化形态。免疫组化染色示CK阳性,P63、SMA阴性;Ki-67阳性指数4例<5%,1例高级别患者为30%。4例随访13~78个月,未见肿瘤复发和转移;1例高级别患者术后10个月死亡。结论腺泡细胞癌好发于女性腮腺,通常为低度恶性,而高级别转化腺泡细胞癌预后差,其临床综合治疗尚须进一步探讨。     

c-kit蛋白和Ki-67表达在涎腺基底细胞腺瘤和腺样囊性癌诊断中的意义

 目的　探讨原癌基因c-kit和细胞核增殖抗原Ki-67的表达在涎腺基底细胞腺瘤和腺样囊性癌诊断中的意义。方法　应用免疫组织化学方法检测18例基底细胞腺瘤和42例腺样囊性癌标本中瘤细胞c-kit和Ki-67的表达。结果　18例基底细胞腺瘤和42例腺样囊性癌中c-kit的表达率分别为72.2 %（13／18）和83.3 %（35／42）,两者差异无统计学意义（χ2＝0.11,P＞0.05）;18例基底细胞腺瘤和42例腺样囊性癌中Ki-67的平均表达率分别为（3.72±1.41）%和（23.81±10.19）%,两者差异有统计学意义（t＝14.145,P＜0.01）。结论　原癌基因c-kit表达对涎腺基底细胞腺瘤和腺样囊性癌的鉴别诊断无意义, Ki-67 对两者鉴别诊断有意义。     

涎腺多形腺瘤与腺样囊性癌中MMP-2的表达差异与MVD的关系

目的　研究基质金属蛋白酶 2 (MMP 2 )在涎腺肿瘤中表达及对微血管密度的影响。探讨其与该肿瘤侵袭和转移的关系。方法　应用免疫组化S P法观察 3 6例涎腺肿瘤石蜡包埋组织中的MMP 2、CD3 4表达。并在CD3 4染色切片上检测间质微血管密度(MVD)。结果　MMP 2在涎腺腺样囊性癌中高表达阳性率 ( 68 2 %) ,明显高于涎腺多形性腺瘤 ( 2 8 6%)。涎腺腺样囊性癌中的MVD的平均值 ( 63 41± 4 43 )明显高于涎腺多形性腺瘤 ( 4 5 43± 4 3 0 )。MMP 2高表达阳性组的MVD的平均值 ( 66 84± 4 65 )明显高于MMP 2表达阴性组 ( 4 4 76± 3 5 3 )。结论　MMP 2促进涎腺肿瘤间质血管生成 ,促进肿瘤的侵袭和转移 ,有可能成为判定涎腺肿瘤生物学行为和预后的指标     

阴囊部皮肤原发性腺样囊性癌1例报告及文献复习

目的：探讨原发阴囊部皮肤腺样囊性癌的临床病理特点,免疫组化及鉴别诊断要点。方法：报道1例原发阴囊部皮肤腺样囊性癌的临床、病理组织学形态和免疫组化特点,并复习相关文献对以上特点进行分析。结果：皮肤的腺样囊性癌较少见,可发生于除掌跖以外的任何部位,中老年好发,平均发病年龄为59岁。原发阴囊部皮肤腺样囊性癌未见报道,镜下肿瘤组织形成特殊的筛状结构,囊腔内常含有阿辛兰（pH5.2）阳性的透明质酸和硫酸化的酸性黏蛋白,瘤细胞间和小叶间周围可见透明嗜酸性基底膜物质的沉积,PAS染色呈阳性。免疫组化CK7、S-100、EMA、P63阳性表达。结论：阴囊皮肤原发腺样囊性癌相对少见,其具有与涎腺腺样囊性癌相同的镜下特征和免疫组化特点,临床表现呈惰性过程,预后相对较好。     

EZH2和Ki-67蛋白在腺样囊性癌中的表达及其临床意义

  目的  研究人涎腺腺样囊性癌组织中EZH2（enhancer of zeste homolog2）和Ki-67的表达及其相关性。  方法  采用免疫组织化学染色法,检测石蜡包埋的42例涎腺腺样囊性癌（salivary adnoid cystic carcinoma,SACC）及5例正常涎腺组织中,多梳组蛋白EZH2和细胞周期蛋白Ki-67的表达水平,分析与临床病理特征之间的关系并探讨二者的相关性。  结果  EZH2在腺样囊性癌组织中的表达显著高于正常涎腺组织（P＜0.05）,EZH2表达阳性率66.67%（28/42）,EZH2表达与肿瘤病理分型及临床分期相关,而与性别、年龄、发病部位不相关,而在5例正常涎腺组织中不表达。在Ki-67阳性的33例腺样囊性癌患者中,25例EZH2表达阳性,表达率75.76%（25/33）,Ki-67阴性表达的9例中,3例EZH2表达阳性,表达率33.33%（3/9）,两者比较差异有统计学意义（P＜0.05）。  结论  EZH2在腺样囊性癌中表达增加且与肿瘤细胞的增殖密切相关,提示腺样囊性癌中EZH2通过其在细胞周期管理中的作用,参与肿瘤细胞的增殖过程。      

Ezrin在涎腺腺样囊性癌组织中的表达

目的:探讨Ezrin在涎腺腺样囊性癌组织中的表达及意义。方法:用免疫组织化学SP法检测Ezrin在涎腺腺样囊性癌组织和正常涎腺组织中的表达,分析其在涎腺腺样囊性癌组织中的表达与肿瘤的侵袭性、复发、转移和预后的关系。结果:Ezrin在涎腺腺样囊性癌和正常涎腺组织中的阳性率表达分别为44.68%和9.09%,P<0.05;在癌细胞中主要为胞质内表达,染色深,而在正常涎腺组织则主要为细胞膜表达,染色浅或阴性。Ezrin的表达强度与有无神经受侵、有无发生局部复发及远处转移相关,P<0.05。Ezrin表达阳性组和阴性组的5年累积生存率分别为66.70%和100.00%,10年累及生存率分别为27.83%和95.00%,阳性组较阴性组预后差,P<0.05。结论:Ezrin的表达强度与涎腺腺样囊性癌的发生、侵袭性、复发和转移性有关,且Ezrin阳性表达预示患者预后不良。     

Histogenesis of adenoid cystic carcinoma of the salivary glands. Light and electronmicroscopic study

This ultrastructural study, based on 12 cases of adenoid cystic carcinoma of the major and minor salivary glands, was conducted to determine the role and extent of participation of myoepithelial cells in their histogenesis. The tumors were composed of four major cell types; intercalated duct, myoepithelial, secretory, and pluripotential reserve/stem cells. The cellular composition of adenoid cystic carcinoma is similar to that in the "terminal tubule" complex stage of a developing salivary gland except that in the tumor the pluripotential reserve/stem cells differentiate predominantly along the intercalated duct cell line rather than secretory cells as in the acinic cell carcinoma. Furthermore, adenoid cystic carcinoma appears to contain a far greater number of myoepithelial cells than acinic cell carcinomas.     

Differential expression of galectin-1 and galectin-3 in benign and malignant salivary gland neoplasms

Galectins are a family of non-integrin beta-galactosidase-binding lectins. Altered expression of galectins has been associated with neoplastic transformation and progression in several human tumors. In this study, we examined the distribution patterns of galectin-1 and galectin-3 in normal (n=45), benign (n=16), and malignant (n=49) salivary gland specimens using immunohistochemistry to determine their diagnostic and/or biological implications in salivary gland tumorigenesis. In normal salivary glands, galectin-3 expression was limited to ductal cells, and galectin-1 was usually faintly detected in ductal cells and strongly positive in myoepithelial cells. In benign tumors, galectin-3 maintained the ductal localization, but galectin-1 showed variable expression in ductal and myoepithelial cells. In malignant tumors, most of the polymorphous low-grade adenocarcinomas and carcinoma ex-pleomorphic adenomas expressed both galectins, whereas adenoid cystic and acinic cell carcinomas showed dramatically reduced galectin-3 expression and heterogeneous galactin-1 staining. Our data demonstrated altered localization and expression of galectin-3, and to lesser extent, galectin-1 in salivary gland carcinomas. These findings may assist in the differential diagnosis of some salivary gland malignancies, especially when using small and limited fine-needle aspiration materials.     

Epidermal growth factor receptor (EGFR) in salivary gland carcinomas: Potentials as therapeutic target

AimsEpidermal growth factor (EGFR) is involved in angiogenesis, cell differentiation, proliferation and progression of many cancers and is an important therapy target in lung and colorectal cancer. To determine the potential applicability of EGFR targeted therapies, EGFR status of over 800 salivary gland tumors of different entities were analyzed on DNA and protein level by FISH and IHC.Materials and methodsA tissue microarray was constructed from 721 carcinomas and 205 adenomas of the salivary gland. EGFR expression and EGFR gene copy number was assessed by means of immunohistochemistry and fluorescence in situ hybridization (FISH). EGFR mutation analysis of exon 19 and 21 was performed in a subset of 107 carcinomas.ResultsPositive immunohistochemical staining (definition?) for EGFR was shown in 324 of 663 (48.9%) salivary gland carcinomas. The frequency was dependent on the tumor entity and ranged from 17.9% (30 of 168 cases) positive immunostaining in acinic cell adenocarcinomas to 85.7% (42 of 49 cases) in Warthin tumors. No EGFR amplification was found by FISH. EGFR mutation analysis of Exon 19 and 21 in 107 salivary gland carcinomas revealed mutations in two acinic cell adenocarcinomas .ConclusionEGFR protein expression is common in salivary gland tumors but is not associated with gene amplification. Activating mutations of EGFR are rare. Nonetheless, selected cases of patients with salivary gland carcinomas might potentially benefit of anti-EGFR therapy.     

酪氨酸激酶B在涎腺腺样囊性癌中的表达及与嗜神经侵袭的关系

目的检测酪氨酸激酶B(TrkB)在涎腺腺样囊性癌(ACC)的表达情况，探讨TrkB与ACC嗜神经侵袭的关系。方法研究对象为28例ACC，3例正常腮腺，3例正常颌下腺，3例正常舌下腺及5例涎腺腺泡细胞癌标本，采用免疫组织化学及图像分析法对组织切片中的TrkB进行检测。结果以病理学表现为标准，28例ACC中的嗜神经侵袭率为46．4％(13／28)，TrkB阳性率为92．8％(26／28)，存在嗜神经现象组中TrkB表达水平明显高于未见嗜神经现象组(P=0．001)。TrkB的表达在正常大涎腺的导管细胞为阳性，而在腺泡细胞癌胞浆内均为阴性。结论TrkB可能作为ACC嗜神经侵袭的生物学标志物。TrkB表达的增高可能是ACC嗜神经侵袭的机理之一。     

Estrogen receptor expression in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma

Estrogen receptor (ER) expression in salivary gland carcinomas is controversial, and most published studies considered no more than 10 cases. We analyzed ER expression by immunohistochemistry in 136 mucoepidermoid carcinomas and 72 adenoid cystic carcinomas. All cases were negative. These results do not support a role for estrogens in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma.     

Mammalian target of rapamycin-dependent acinar cell neoplasia after inactivation of Apc and Pten in the mouse salivary gland: implications for human acinic cell carcinoma

Cross-talk between the canonical Wnt and mammalian target of rapamycin (mTOR) signaling pathways occurs at multiple levels in the cell and likely contributes to the oncogenic effects of these pathways in human cancer. To gain more insight into the interplay between Wnt and mTOR signaling in salivary gland tumorigenesis, we developed a mouse model in which both pathways are constitutively activated by the conditional inactivation of the Apc and Pten tumor suppressor genes. Loss of either Apc or Pten alone did not cause tumor development. However, deletion of both genes resulted in the formation of salivary gland tumors with 100% penetrance and short latency that showed a remarkable morphologic similarity to human acinic cell carcinoma. Treatment of tumor-bearing mice using the mTOR inhibitor rapamycin led to complete regression of tumors, indicating that tumor growth was dependent on continued mTOR signaling. Importantly, we found that human salivary gland acinic cell carcinomas also express markers of activated mTOR signaling. Together, these results suggest that aberrant activation of mTOR signaling plays a pivotal role in acinar cell neoplasia of the salivary gland. Because rapamycin analogues are approved for treating other types of human malignancies, our findings suggest that rapamycin therapy should be evaluated for treating patients with salivary gland acinic cell carcinoma.     

Clinical and pathologic prognostic features in acinic cell carcinoma of the parotid gland

BACKGROUND:

To the authors' knowledge, the indications for adjuvant treatment in acinic cell carcinoma (AciCC) of the parotid gland have not been elucidated to date. The aim of the current study was to determine patterns of failure and adverse prognostic features.

METHODS:

Between March of 1989 and August of 2006, 35 patients underwent surgery at Memorial Sloan‐Kettering Cancer Center for AciCC of the parotid gland and had their clinical and pathologic features retrospectively analyzed at the primary site. All cases were reviewed by 2 head and neck pathologists. Five‐year estimates of survival outcomes were performed, followed by univariate analysis of potential prognostic features.

RESULTS:

The T classifications were as follows: T1 in 46% of patients, T2 in 23% of patients, T3 in 18% of patients, and T4 in 9% of patients. Three patients had cervical lymph node involvement. All patients underwent surgery as their primary treatment. Approximately 63% of patients (n = 22) received radiation treatment. The median follow‐up time for surviving patients was 59.9 months. Five‐year estimates of disease‐free survival (DFS), overall survival (OS), and local control were 85%, 90%, and 90%, respectively. Of the clinical variables tested, clinical extracapsular extension (ECE), facial nerve sacrifice, and lymph node involvement were found to be significantly associated with a detriment in DFS and OS (P < .05). Positive surgical margins, histologic ECE, >2 mitoses per 10 high‐power fields (HPF), atypical mitosis, vascular invasion, perineural invasion, pleomorphism, and necrosis were associated with adverse DFS (P < .05). All of these variables except for vascular invasion (P = .377) and perineural invasion (P = .07) were associated with OS. If high‐grade tumors were defined on the basis of high mitotic activity (>2 mitoses/10 HPF) and/or tumor necrosis, high‐grade carcinomas had a significantly lower DFS and OS (P = .001).

CONCLUSIONS:

AciCC had a low treatment failure rate, and a large number of patients could be considered candidates for surgery only. A histologic grading system was devised to help stratify patients for adjuvant treatment. Cancer 2009. © 2009 American Cancer Society.     

Genetic alterations in salivary gland cancers

Salivary gland cancers are an incredibly heterogeneous group of tumors that include 24 histologically distinct tumor types. The use of new genetic methods has paved the way for promising advancements in our understanding of the molecular biology underlying each type of tumor. The objective of this review was to highlight common oncogenes, tumor suppressor genes, and cytogenetic and epigenetic changes associated with the most common tumor types: mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, mammary analogue secretory carcinoma, hyalinizing clear cell carcinoma, carcinoma ex pleomorphic adenoma, and acinic cell carcinoma. Recent insights into the pathogenesis of each cancer subtype have helped better define and classify these tumors. Further research in salivary gland cancers should focus on determining the key genes involved in the tumorigenesis of each distinct malignancy and identifying individualized chemotherapies directed at these targets. Cancer 2016;122:1822–31 . © 2016 American Cancer Society.     

Implications of methylation patterns of cancer genes in salivary gland tumors.

PURPOSE: We investigated the methylation status and protein expression of four tumor suppressor genes to determine their role in salivary gland tumorigenesis. EXPERIMENTAL DESIGN: We performed methylation-specific PCR and protein analyses of 29 normal salivary glands, 23 benign, and 79 malignant salivary gland neoplasms to determine the pattern and potential diagnostic and/or biological role of the RASSF1, RARbeta2, DAPK, and MGMT tumor suppressor gene methylation in these tumors. RESULTS: No methylation was detected in the normal tissues. Methylation occurred in 9 of 23 (39.1%) benign tumors; 3 (25.0%) pleomorphic adenomas and 6 (66.7%) Warthin's tumors at the MGMT, DAPK, or RASSF1 genes. Methylation occurred in 33 of 79 (41.8%) malignant tumors; 8 (30.8%) adenoid cystic carcinomas, 6 (33.3%) mucoepidermoid carcinomas, 6 (42.9%) acinic cell carcinomas, and 13 (62.0%) salivary duct carcinomas. RASSF1 and RARbeta2 represented 75.8% of methylation events occurring most frequently in salivary duct and acinic cell carcinomas. Overall, we found no significant correlation between protein expression and methylation status of individual genes, but observed low or absent protein expression in several methylated tumors. Significant correlations were found between methylation and aggressive malignant phenotypes (P = 0.0004) and age (P = 0.05). Conclusions: (a) Benign and malignant salivary tumors differed in the frequency and pattern of gene methylation; (b) high-grade carcinomas were significantly methylated compared with low-grade phenotypes; (c) RASSF1 and RARbeta2 were highly methylated in malignant tumors and can be targeted for therapy; and (d) methylation pattern may serve as a diagnostic and biological marker in assessing these tumors.     

Adenoid cystic carcinoma of the buccal vestibule: A case report and review of the literature

Minor salivary gland tumors of the buccal vestibule are relatively rare. Adenoid cystic carcinoma is the fifth most common salivary gland malignancy following mucoepidermoid carcinoma, adenocarcinoma not otherwise specified (NOS), acinic cell adenocarcinoma and polymorphous low-grade adenocarcinoma (PLGA). Greater than half of adenoid cystic carcinomas occur in the parotid and submandibular glands. The most common intraoral site is the palate. Adenoid cystic carcinoma tends to have a protracted clinical course with wide infiltration and late distant metastases. We present a case of an adenoid cystic carcinoma of the buccal vestibule in a 59-year-old Caucasian female patient that she had been aware of for 15 years.